3-Azetidinols undergo facile alkylative ring opening when treated with phenols at elevated temperatures to produce aryloxypropanolamines (use in the treatment of hypertension, angina pectoris, and cardiac arrhythmia) in excellent yield. Most difficulties preventing commercial utilization of this method been overcome. The electronic factors operative in the azetidinols have been elucidated by experiment and more recently by molecular modeling. Nevertheless, the phenol's electronic factors have been investigated, and some difficulties remain in the preparation of the azetidinols. The specific aims of the proposed research are to: 1) increase the yields of 1-alky1-3-azetidinols--the hurdle preventing commercial utilization of this method, 2) gain a deeper understanding of the mechanism of the alkylative ring opening which produces the aryloxypropanolamines, 3) understand the factors operative at the beta-receptor, and 4) investigate alkylation of adenine, quinine, and cytosine by azetidines and azetidinols-- alkylation of these nucleotides may be a means of preventing cell division and could have consequences in treating cancer and some viral infections. 1) The primary difficulty in preparation of azetidinols seems to involve ring opening of epichlorohydrin by amines. Steric and electronic factors operative in the amine in the ring opening of epichlorohydrin are currently being investigated by HPLC kinetic studies. Ring closure of 1-amino-3-chloro-2- propanols to azetidines will also be investigated in order to further optimize yields. 2) Ring opening of azetidinols by phenols will be investigated by kinetic studies followed by HPLC. Semi-empirical calculations in this respect are nearing completion, and ab initio calculations have been initiated. 3) Molecular modeling, NMR, and FT-IR investigations will be used to more fully elucidate conformational preferences in aryloxypropanolamines and the mechanism by which compounds bind at the beta-receptor. 4) While not part of our original research goals, the possibility of alkylating nucleotides by means of azetidines and azetidinols will be investigated. Two students and a technician will be involved in this research. They will gain training in advanced chemical principles, laboratory operations, application of spectroscopic and chromatographic methods of analysis, interpretation of kinetic and quantum mechanics calculations, and gain valuable technical communications skills.